Human natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGL). The majority of LGL form lytic conjugates with a wide variety of NK-susceptible target cells. The target cell structures involved in NK recognition is being studied and purified. This structure, isolated and partially purified from K562, has been shown to be a glycoprotein of 30-150,000 M.W. Maximal activity in a binding inhibition assay was seen when target structures were associated with lipids. NK cytotoxic factors (NKCF) are being examined for specificity and their mechanism of action. Three distinct steps have been defined for NKCFs; a) production, b) binding to targets, and c) subsequent target lysis. With procedures able to independently measure these events, a variety of agents which have been reported to inhibit NK cell-mediated killing are being tested to determine their site of action. These NKCFs are produced by LGL and have a general specificity pattern similar to intact killer cells. Fresh LGL subpopulations, cultures, and clones of LGL are being tested for reactivity against a variety of NK targets, to identify subsets that demonstrate functional selectivity. In addition, LGL have been shown to produce IFN-Alpha and Beta in response to target cells or lectin. Additional lymphokines (interleukin 1 and 2, B-cell growth factor) and the LGL subset producing them, are being examined.